Cetuximab: clinical results in colorectal cancer

In recent years, the introduction of targeted therapies into clinical practice seems to offer incremental benefits in the treatment of metastatic colorectal cancer (mCRC), mainly when they are employed in combination with optimal chemotherapy and/or radiotherapy. In this paper, we focus on Cetuximab and its role in the treatment of mCRC.

FOLFIRI regimen in advanced colorectal cancer: the experience of the Gruppo Oncologico dell'Italia Meridionale (GOIM)

Purpose: To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy. Patients and methods: Patients entered in three consecutive trials of the GOIM (protocols no. 9706, 9901, and 2301) were reported in this analysis. A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen: Irinotecan 180mg/m 2 on day 1 with LV5FU2 regimen (LV at 100mg/m 2 administered as a 2-hour infusion before FU at 400mg/m 2 as an intravenous bolus injection, and FU at 600mg/m 2 as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2); the treatment was repeated every 2 weeks. Results: 287 patients entered in th…

Cetuximab in squamous cell head and neck carcinomas.

The epidermal growth factor receptor (EGFR) antagonist, cetuximab, has recently been shown to enhance the effects of radiotherapy, and reports to date indicate that this effect occurs without any change in the pattern and severity of toxicity usually associated with head and neck radiation and/or chemotherapy (CT) administration. Moreover, several studies have reported that the expression of EGFR is strongly linked to poor outcome in patients undergoing therapy. Therefore, the presence of the EGFR in almost all cases of head and neck carcinoma offers a new therapeutic opportunity to most patients. In this paper, we report a review of the major studies dealing with the use of cetuximab in ad…

Clinical results of EGFR-targeted therapies in advanced colorectal cancer

Abstract This paper is an updated review of the pre-clinical rationale and clinical results of new EGFR-targeted agents – cetuximab and panitumumab – employed in the management of advanced/ metastatic colorectal cancer. The addition of either biologic agent or last generation standard chemotherapy regimens – FOLFIRI and FOLFOX – has yielded better results as compared to those reported for chemotherapy alone. These results have been obtained without a significant increase in severe toxicity with the exception of skin side-effects.

Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: Results of a multicenter phase II study

Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.

<i>Objectives:</i> FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. <i>Methods:</i> Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m<sup>2…

Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib.

Abstract Introduction. Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients. Materials and Methods. All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response …

FOLFIRI with or without celecoxib in advanced colorectal cancer: a randomized phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)

Background The aim of the study was to verify the efficacy and safety of the addition of celecoxib to FOLFIRI combination therapy in patients affected by advanced colorectal cancer. Patients and methods Eighty-one chemotherapy-naive patients entered in this randomized phase II trial of the GOIM (protocol no. 2301). Patients were randomized to receive FOLFIRI regimen (arm A): irinotecan 180 mg/m2 on day 1 with LV5FU2 regimen (LV at 100 mg/m2 administered as a 2-h infusion before FU at 400 mg/m2 as an intravenous bolus injection, and FU at 600 mg/m2 as a 22-h infusion immediately after 5-FU bolus injection on day 1 and 2); or FOLFIRI plus celecoxib 400 mg twice daily for 14 days (arm B). Both…

Correlation between basal bilirubin levels and survival in advanced colorectal carcinoma treated with CPT-11-based chemotherapy: A study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.)

AbstractBackgroundThis study was carried out to evaluate total basal bilirubin levels as a predictive factor for survival and toxicity in patients with advanced colorectal carcinoma treated with CTP-11-based regimens.Patients and methodsThe analysis was carried out on a data base including 287 patients affected by advanced colorectal carcinoma all treated with CPT-11 plus bolus and continuous venous infusion intravenous folinic acid and 5-fluorouracil on a biweekly schedule (FOLFIRI regimen). Patients were divided into four groups according to basal bilirubin levels as follows: 0.50 and 1.00 and 1.50mg/dl. Analysis of overall median survival and time-to-progression were correlated to perfor…

Epidoxorubicin and double biochemical 5-fluorouracil modulation with folinic acid and human lymphoblastoid interferon in advanced gastric carcinoma: a multicentric phase II study of the Southern Italy Oncology Group (GOIM).

In our previous randomized trial of advanced gastric cancer patients, the addition of epirubicin (EPI) to 5-fluorouracil (FU) with folinic acid (FA) resulted in an improved response rate and survival in the responder patients. Preclinical studies also showed an enhancement of FU and anthracyclines with interferon. To evaluate the possibility of human lymphoblastoid interferon (IFN) to enhance the therapeutic activity of the FA-FU + EPI combination regimen, 39 advanced gastric cancer patients received: FU at 375 mg/m2 i.v. immediately after FA (l-isomer form) at 100 mg/m2 i.v. for 5 consecutive days; EPI at 60 mg/m2 i.v. on day 1, and IFN 3 MU s.c. for 7 consecutive days, starting 2 days bef…

Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice.

Background: In daily clinical practice second-line chemotherapy (SLCT) is frequently given to patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy without solid scientific support. Patients and methods: A retrospective survey was carried out including 42 patients. Patients received standard FOLFOX4 regimen biweekly until progression or unacceptable toxicity. Results: Six partial responses (14%) and 16 stabilizations (38%) were recorded for a tumor growth control rate of 57%. The median time to progression (TtP) was 4 months (range 1–7 months), and median overall survival (OS) was 6.7 months (range 2–9 months). A stabilization of performance status (PS) …

5-Fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: A multicenter randomised phase II study of the Southern Italy Oncology Group

The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial.A total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of ageor = 70 and75 years) only on day 1 immediately before LV5FU2 th…

Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)

Background The aim of the study was to test the clinical efficacy and toxicity profile of gemcitabine (GEM) in combination with cisplatin (CDDP) in a series of patients affected by unresectable and/or metastatic biliary tree carcinoma (BTC) previously untreated with chemotherapy. Patients and methods Overall 38 consecutive patients who satisfied eligibility criteria (10 with gall-bladder carcinoma and 28 with bile duct carcinoma) were included in this phase II study. Median age was 61 years with median PS 1. Treatment included GEM 1000 mg/m2/week as 30 min i.v. on days 1 and 8, and CDDP 75–80 mg/m2 on day 1 with adequate hydration protocol and forced diuresis. Treatment was repeated every 3…

Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…

Irinotecan Plus Bolus/Infusional 5-Fluorouracil and Leucovorin in Patients With Pretreated Advanced Pancreatic Carcinoma

Patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy are still in relatively good clinical conditions and may still require second-line chemotherapy, which is frequently administered in daily clinical practice given to without solid scientific support.A retrospective survey was carried out including 40 patients with stage III or IV gemcitabine-refractory pancreatic carcinoma. Patients received standard FOLFIRI regimen biweekly until progression or unacceptable toxicity. Response evaluation criteria in solid tumors and National Cancer Institute common toxicity criteria were employed respectively for response and toxicity assessment.Six partial responses …

Irinotecan (CPT-11) and Mitomycin-C (MMC) as Second-Line Therapy in Advanced Gastric Cancer

Objective The aim of this study was to evaluate the activity and toxicity of a combination regimen of CPT-11 and mitomycin-c as second-line chemotherapy for pretreated patients with advanced, metastatic, or both, gastric adenocarcinoma. Materials and methods Patients with pretreated metastatic disease or early relapsed after adjuvant chemotherapy were enrolled. Entry criteria included histologic/cytologic diagnosis of gastric adenocarcinoma, age 18 to 75 years, performance status > or =70 (Karnofsky scale), bi-dimensionally measurable disease. Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks. The disease …

Epirubicin, Folinic Acid, Fluorouracil, and Etoposide in the Treatment of Advanced Gastric Cancer

In the authors' previous experience, the addition of epidoxorubicin to the FA-FU regimen obtained a better response rate than that of FA-FU alone in patients with advanced gastric cancer. Furthermore, considering the good efficacy and mild toxicity observed with the addition of etoposide to the FA-FU combination in the German study, the authors conducted a trial to explore the efficacy and tolerability of the ELFE regimen (epirubicin, folinic acid, fluorouracil, and etoposide) in previously untreated advanced gastric cancer patients. Of the 55 patients entered, 51 were evaluable for efficacy. Four complete responses (8%) and 21 partial responses (41%) were observed, with an overall response…

Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations…